Viral pseudo-enzymes activate RIG-I via deamidation to evade cytokine production

Molecular Cell
Shanping HePinghui Feng

Abstract

RIG-I is a pattern recognition receptor that senses viral RNA and is crucial for host innate immune defense. Here, we describe a mechanism of RIG-I activation through amidotransferase-mediated deamidation. We show that viral homologs of phosphoribosylformylglycinamidine synthetase (PFAS), although lacking intrinsic enzyme activity, recruit cellular PFAS to deamidate and activate RIG-I. Accordingly, depletion and biochemical inhibition of PFAS impair RIG-I deamidation and concomitant activation. Purified PFAS and viral homolog thereof deamidate RIG-I in vitro. Ultimately, herpesvirus hijacks activated RIG-I to avoid antiviral cytokine production; loss of RIG-I or inhibition of RIG-I deamidation results in elevated cytokine production. Together, these findings demonstrate a surprising mechanism of RIG-I activation that is mediated by an enzyme.

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Citations

Sep 20, 2015·Current Opinion in Virology·Jun ZhaoPinghui Feng
Sep 2, 2016·Frontiers in Microbiology·Brandon CieniewiczLaurie T Krug
Jan 18, 2018·Journal of Neurochemistry·Colleen A MangoldMoriah L Szpara
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Feb 19, 2016·Journal of Virology·Jun ZhaoPinghui Feng
Jul 27, 2017·European Journal of Immunology·Yilong ZhouBaoxue Ge
Sep 6, 2020·The FEBS Journal·Ting-Yu WangPinghui Feng
Aug 31, 2016·The Journal of Microbiology·Nari KimJoo-Yeon Yoo
Dec 5, 2019·Frontiers in Microbiology·Jessica CarrierePinghui Feng
Mar 24, 2020·Nature Reviews. Immunology·Jan Rehwinkel, Michaela U Gack
Jan 18, 2017·Frontiers in Immunology·Yiliu LiuRongtuan Lin
May 21, 2019·Journal of Medical Virology·Sheng-Na LiLiang-Guo Xu
Sep 11, 2019·Journal of Clinical Medicine·Florian Full, Armin Ensser
Aug 15, 2019·Science Signaling·António J M RibeiroPatrick A Eyers
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Apr 24, 2020·Cell Metabolism·Jun ZhaoPinghui Feng
Sep 30, 2021·Annual Review of Virology·Yiping WangLaurie T Krug

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